Podolak Jennifer, Eilers Kristi, Newby Timothy, Slottke Rachel, Tucker Erin, Olson Susan B, Lue Hui-Wen, Youngren Jack, Aggarwal Rahul, Small Eric J, Graff Julie N, Alumkal Joshi J, Beer Tomasz M, Thomas George V
Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA.
Oncotarget. 2017 Mar 13;8(42):71447-71455. doi: 10.18632/oncotarget.16169. eCollection 2017 Sep 22.
Increased activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the gene is a common mechanism by which mCRPC increase activity. To determine whether amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence hybridization (FISH). gene status in CTCs showed strong concordance with gene status in matched tissue samples in 24 of 25 patients (Correlation: 96%; Kappa: 0.83; Sensitivity: 100%, Specificity: 83%). Our work demonstrates that amplification is conserved between CTCs and biopsies and that CTCs can serve as non-invasive surrogate to document amplification in mCRPC.
在来自同一患者的空间上不同的转移性肿瘤中，已显示活性增加，这表明转移性去势抵抗性前列腺癌（mCRPC）需要谱系特异性依赖性。该基因的扩增是mCRPC增加活性的常见机制。为了确定循环肿瘤细胞（CTC）中的扩增是否可以补充接受mCRPC治疗的男性的转移性组织活检，我们开发了一种新颖的两步法来分离CTC，随后通过荧光原位杂交（FISH）分析同一患者的CTC和匹配活检组织中的扩增状态。25例患者中有24例的CTC中的基因状态与匹配组织样本中的基因状态显示出强烈的一致性（相关性：96％； Kappa：0.83；敏感性：100％，特异性：83％）。我们的工作表明，CTC和活检之间的扩增是保守的，并且CTC可以作为无创替代物来记录mCRPC中的扩增。
